It is well known that the new network of blood vessels occurs in cancer and the network supplies nutrients that sustained the uncontrolled growth of abnormal cells in the body. However, it has been shown that these blood vessels are distinct from those of normal healthy tissues. The differences can affect the delivery and therefore the efficacy of anti-cancer therapy that targets the cancer cells, e.g, solid tumors.
The network of blood vessels and constituents in tumors has abnormal structures and functions. For example, the network of blood vessels have irregular morphology and pattern; the blood vessels tend to be thicker and have large clumps of tumor endothelial cells (TECs), the blood vessels are hyperpermeable (“leaky”), and the TECs have abnormally high basal level of active Rho, increased rate of cell migration, and aberrant mechanosensory response and orientation to external mechano-stimuli such as stretch stress when compared to non-cancer derived, normal endothelial cells (nECs). These abnormal TECs lead to abnormal angiogenesis in tumors, resulting in the irregular networks and “leaky” blood vessels. Many solid tumors show an increased interstitial fluid pressure (IFP) due to the irregular network, which forms a physical barrier to drug delivery, particular to the interior of a solid tumor. For example, the hyperpermeability of the tumor blood vessels creates a situation where a therapeutic effective amount of anti-cancer therapy fails to reach the target area because a substantial amount of the anti-cancer therapy has leaked out of the blood vessels enroute to the interior of a solid tumor. In addition, the irregular network affects blood flow rate and can impede a sustained delivery of an anti-cancer therapy to the target area. Therefore, innovations that address the abnormal angiogenesis, blood vessel network and abnormal characteristics of TECs in cancer can potentially impact the effectiveness of anti-cancer therapies.